Radiolabeled amino acids are an important class of tumor imaging agents that target the increased rates of amino acid transport that occur in many types of tumor cells. A number of radiolabeled amino acids including L-[11C]methionine, (2-[18F]fluoroethyl)-L-tyrosine (FET), 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine (FDOPA), 3-[123I]iodo-a-methyl-L-tyrosine (IMT) have proven utility for imaging gliomas in human patients. (Singhal, T, et al. Mol. Imaging. Biol. 10:1-18, 2008; Langen, K. J., et al. Nucl. Med. Bio 33: 287-294, 2006; Chen, W., et al. J. Nuc. Med. 47: 904-911, 2006; Langen, K. J., et al. Nucl. Med. Biol. 29: 625-631, 2006; McConathy, J., et al. Cancer Metastasis Rev. 27: 555-573, 2008). These tracers have improved sensitivity and specificity relative to 2-[18F]fluoro-2-deoxy-D-glucose (FDG) for detecting brain gliomas, particularly in the setting of recurrence after treatment. Radiolabeled amino acids also can increase the diagnostic yield of stereotactic biopsy and provide better delineation of tumor volumes for treatment planning than contrast enhanced magnetic resonance (MR) imaging alone. Radiolabeled amino acids may also be useful for monitoring response to therapy and differentiating low grade from high grade gliomas. Amino acids may also be useful in imaging tumors outside of the brain. For example, [18F]FDOPA appears to be useful for imaging carcinoid and other neuroendocrine tumors, and anti-3-[18F]fluoro-1-amino-1-cyclobutane carboxylic acid (FACBC) has shown promising preliminary results for imaging prostate cancer. (Becherer, A., et al. J. Nucl. Med. 45: 1161-1167, 2004; Montravers, F., et al. J. Nucl. Med. 47: 1455-1462, 2006; Schuster, D. M., et al. J. Nucl. Med. 48: 56-63, 2007; Oka, S., et al. J. Nucl. Med. 48: 46-55, 2007).
Amino acids enter cells via membrane-associated carrier transport proteins. Over 20 mammalian amino acid transport systems have been described with varying substrate specificities, pH dependence, sodium dependence and regulatory mechanisms. A number of amino acid transport subtypes including L-type amino acid transporter 1 (LAT1) and amino acid transporter type 2 (ASCT2) have been shown to be upregulated in various human tumors including breast cancers and gliomas, and their presence may have prognostic significance. (Fuchs, B. C., et al. Am. J. Physiol. Cell. Physiol. 293: C55-C63, 2007; Fuchs, B. C., et al. Semin. Cancer Biol. 15: 254-266; Esseghir, S., et al. J. Pathol. 210: 420-430, 2006; Nawashiro, H., et al. Int. J. Cancer 119: 484-492, 2006). The leucine-preferring amino acid transport system (system L) and to a lesser extent the alanine-preferring amnion acid transport system (system A) have been the major focus of radiolabeled amino acid development for positron emission tomography (PET) and single photon computed tomography (SPECT). However, health care professionals are in need of radiolabeled amino acids suitable for PET and SPECT that target amino acid transport systems other than system L and system A, such as cationic amino acid transport.